The present study was designed to investigate the role of retinoic acid in the prevention or development of breast cancer. Preformed vitamin A, or retinol, is found in animal foods such as liver and whole milk, and in some fortified processed foods. Certain carotenoids such as beta-carotene are also efficiently converted into retinol. Once retinol is converted into its bioactive form, retinoic acid, it plays important roles in cell division, cell death, and cell differentiation. In the study, retinoic acid was found to regulate a network of tumor suppressor genes governing cell death, proliferation, differentiation, migration, and invasion through retinoic acid receptor alpha. Retinoic acid can exert a double-edged action according the authors: it can either inhibit or promote the formation of cancer according to the functional status of one of its receptors, retinoic acid receptor alpha. In fact, retinoic acid was found capable of exerting a clear tumor-promoting action (concomitant with epigenetic silencing of the tumor suppressor gene network) due to loss/functional inhibition of retinoic acid receptor alpha. This raises the question whether dietary sources of retinoic acid, or retinoic acid precursors, can also promote can development in cells with impaired retinoic acid receptor alpha. To perform the investigation, athymic female nude mice were implanted with subcutaneous xenograft tumors consisting of one of two clonal lines of estrogen receptor alpha positive (ERα+) T47D breast cancer cells: one with a functional retinoic acid receptor alpha-regulated gene network (T47DLXC5) and one without functional retinoic acid receptor alpha (T47DDNC8). The mice were administered a diet with either retinoic acid (5 or 10 mg/kg) or retinol (50 mg/kg) for six weeks. These diets were found to induce opposite effects on xenograft tumor growth, depending on whether the tumor cells had functioning retinoic acid receptor alpha. T47DDNC8 xenograft tumors were stimulated to grow and metastasize to distant sites by both retinoic acid and retinol, whereas the growth of T47DLXC5 xenograft tumors was inhibited by retinoic acid and retinol, and the cells did not become invasive. In breast cancer, retinoic acid receptor alpha function often is impaired due to a variety of upstream causes, including faulty retinoic acid transport by CRABP2 onto the retinoic acid receptor alpha and/or loss of ERα, a pivotal retinoic acid receptor alpha transcriptional regulator. The authors comment that early detection of epigenetic silencing of tumor suppressor genes of the retinoic acid receptor alpha network may be used to prevent tumorigenic effects of dietary sources of retinoic acid.

The present population-based case-control study was designed to investigate the associations between intakes of polyphenols and N-nitroso compounds (NOCs) and gastric cancer. NOCs are known potent animal carcinogens and suspected human carcinogens. The primary source of NOC exposure for most people may be endogenous formation, a biochemical process that can be inhibited by dietary polyphenols. The study, which was carried out in Mexico City during 2004 and 2005, included 257 confirmed cases of gastric cancer and 478 cancer-free controls. A food frequency questionnaire was used to assess intake of polyphenols, nitrates and nitrites. High intakes of cinnamic acids, secoisolariciresinol and coumestrol were found to be associated with an approximately 50% reduction in risk of gastric cancer. On the other hand, high intake of total nitrite, as well as nitrate and nitrite from animal sources, was found to increase the risk. Approximately double the risk was observed among persons with both low intake of cinnamic acids, secoisolariciresinol or coumestrol and high intake of animal-derived nitrates or nitrites, compared to those with high intake of these polyphenols and low intake of animal nitrates or nitrites. The results were comparable for both the intestinal and diffuse types of gastric cancer. The authors conclude that cinnamic acids, secoisolariciresinol and coumestrol have a protective effect against gastric cancer, and that these polyphenols may reduce gastric cancer risk through inhibition of endogenous nitrosation. The main sources of these polyphenols in the diets of the participants were pears, mangos and beans for cinnamic acids; beans, carrots and squash for secoisolariciresinol and legumes for coumestrol.

Some population studies have found a diet high in vegetables to be associated with less likelihood of recurrence in breast cancer survivors. Carotenoids, which are found primarily in vegetables and fruit, are thought to have biological activities that may specifically reduce the progression of breast cancer. The present study was designed to examine the relationship between plasma carotenoids at enrollment and at points in time one, two or three, four, and six years, and breast cancer-free survival. Cases were 3,043 participants in the Women's Healthy Eating and Living Study who had been diagnosed with early-stage breast cancer. The primary end point was time to either a second breast cancer recurrence or a new primary breast cancer. The analysis was adjusted for prognostic and other confounding factors. 508 (16.7%) breast cancer events (recurrence or new primary breast cancer) took place over a median 7.12 years of follow up. Compared with the lowest third, the hazard ratio for the medium/high plasma carotenoid tertiles was 0.67 (95% confidence interval, 0.54-0.83). The authors conclude that higher biological exposure to carotenoids was associated with greater likelihood of breast cancer–free survival when assessed over the time frame of the study.

The present hospital-based case-control study was designed to examine the associations between fruit and vegetable consumption and risk of breast cancer. Four hundred and thirty-eight breast cancer cases in Guangdong, China were matched to 438 controls by age (5-year groupings) and location (rural/urban). Dietary factors were ascertained by interviews using a validated food frequency questionnaire. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated after adjusting for various potential confounders. Total overall fruit and vegetable consumption was found to be inversely associated with risk of breast cancer. The odds ratio of the highest fourth relative to the lowest quartile of total fruit consumption was 0.53 (95% CI 0.34-0.82) and for vegetable intake was 0.28 (95% CI 0.18-0.43). Consumption of banana, watermelon/papaya/cantaloupe, dark green leafy vegetables, cruciferous vegetables, carrots, and tomatoes were each significantly associated with lower breast cancer risk. An inverse association with breast cancer risk also was found for intakes of vitamin A, carotene, vitamin C, vitamin E, and fiber. The authors conclude that greater consumption of vegetables and fruits is associated with a lower risk of breast cancer among Chinese women residing in Guangdong.

The present study was designed to evaluate consuming carrot juice as a strategy to increase carotenoids in the blood to levels associated with protection against breast cancer. Breast cancer recurrence after breast cancer treatment may be lower among women with higher plasma carotenoid levels. Thirty-three breast cancer survivors participated in a randomized, controlled trial in which they drank 8 fluid ounces of fresh carrot juice each day for three weeks. Study participants were assigned randomly to consume either purple (n=23) or orange (n=10) carrot juice. Average baseline carotenoid levels at the beginning of the trial were 1.24±0.73 μmol/L for total carotenoids, 0.11±0.12 μmol/L for α-carotene, and 0.39±0.38 μmol/L for β-carotene. At the end of three weeks, levels increased significantly (p<0.001) to 4.80±1.91 μmol/L, 1.52±0.75 μmol/L, and 2.03±1.05 μmol/L, respectively. The average change in carotenoids did not differ significantly between the two carrot types. Average total plasma carotenoids reached levels previously shown to be protective against breast cancer recurrence (4.19 μmol/L). The authors conclude that daily consumption of 8 oz. of carrot juice may represent a simple and effective dietary strategy to protect against recurrence among breast cancer survivors.

The present study was designed to determine how cooking influences bile acid binding of various vegetables under human physiologic conditions. The cholesterol-lowering potential of some foods and food components have been shown to be related to their bile acid-binding ability. Also, secondary bile acids have been found to increase the risk of cancer. Therefore, bile acid–binding potential is related both to lowering the risk of heart disease and to cancer prevention. Simulating gastric and intestinal digestion, 8 replicate incubations were conducted for each treatment, which included a substrate only, a bile acid mixture only, and 6 substrate plus bile acid mixture. Cholestyramine, a bile acid-binding drug with cholesterol-lowering action, was the positive control treatment, and cellulose was used as the negative control. Relative to cholestyramine, in vitro bile acid binding on a dry matter basis was found to be 18% for beets, 16% for okra, 14% for eggplant, 10% for asparagus, 8% for carrots, 7% for green beans, 6% for cauliflower, and 1% for turnips. The results show significantly different (P ≤ .05) bile acid binding on a dry matter basis of these vegetables. Steam cooking was found to significantly improve in vitro bile acid binding of beets, eggplant, asparagus, carrots, green beans, and cauliflower compared with the experimental bile acid-binding values for these vegetables when uncooked.

The current study examined the effects of vitamin A within a human food-based diet (i.e., whole food diet) on sexual maturation, mammary gland development, and sensitivity to carcinogenesis in laboratory rats. A prior study using an adolescent rat model for breast cancer found an increase in mammary tumor occurrence in animals fed a chemopreventive dose of vitamin A. Animal models for nutrient-cancer interactions using strictly defined diets do not replicate the complexity of the human diet and may not be adequate to investigate food patterns associated with cancer risk in humans. Starting at age 20 days, female rats were fed either a whole-food diet with adequate levels of vitamin A (control diet), a diet with a 5.5-fold increase in vitamin A from fruits and vegetables, or a diet with a 6.2-fold increase in vitamin A provided as retinyl palmitate. The dietary intervention period was from age 20 days to age 63 days in order to determine the effect of the diets on pubertal mammary gland development. On day 66, the rats were injected with the mammary carcinogen 1-methyl-1-nitrosourea. Compared with adolescent rats that consumed the control diet, consumption of the fruits and vegetables and vitamin A diets were found to reduce mammary tumor multiplicity (relative risk 0.7, P 0.002), which was associated with a decrease in alveolar gland development. The fruits and vegetables diet suppressed the onset of sexual maturation (P < 0.001) and inhibited markers of mammary alveologenesis more than the vitamin A diet. The authors conclude that the amount and source of vitamin A consumed by adolescent female rats can influence the onset of puberty, mammary gland alveolar development, and breast cancer risk. The study highlights the relevance of using whole-food diets to evaluate the impact of dietary factors in cancer prevention.

The current study was designed to investigate the influence of oleic, linoleic and eicosapentaenoic acids on the bioavailability of β-carotene, including plasma β-carotene response and its conversion to retinol (vitamin A). The study was conducted by using single (9 hour time course) and repeated (10 days) dose administrations in rats. After a single dose, the levels of plasma β-carotene and retinyl palmitate in the oleic acid and eicosapentaenoic acid groups were higher by 13, 7 and 11, 6 folds than in the linoleic acid group (p < 0.05). The liver β-carotene level in the oleic acid and eicosapentaenoic acid groups were higher by 3 and 1.2 folds than in the linoleic acid group (p < 0.05). After 10 days' repeated dose, the plasma β-carotene and retinyl palmitate levels in oleic acid (6.2%, 51.7%) and eicosapentaenoic acid (25.4%, 17.23%) groups were higher than in the linoleic acid group (p < 0.05). The liver β-carotene level in oleic acid (21.2%) and eicosapentaenoic acid (17.6%) groups also were higher than in the linoleic acid group (p < 0.05). In both the experiments, the activity of β-carotene 15,15′-dioxygenase in the intestinal mucosa and plasma triglyceride levels were also found to be higher in the oleic acid and eicosapentaenoic acid groups than in the linoleic acid group. β-carotene excreted through the urine and feces of the oleic acid and eicosapentaenoic acid groups was lower than that of the linoleic acid group. The authors conclude that the results demonstrate an improved absorption and metabolism of β-carotene when fed a diet supplemented with oleic acid or eicosapentaenoic acid compared to linoleic acid.

The present nested case-control prospective study of women enrolled in the Nurses’ Health Study was designed to assess the associations between plasma α-carotene, β-carotene, β-cryptoxanthin, lycopene, lutein/zeaxanthin, retinol, α-tocopherol, and γ-tocopherol and the risk of breast cancer. 969 cases of breast cancer diagnosed after blood had been drawn and prior to June 1998 were individually matched to controls. The multivariate risk of breast cancer was found to be 25% to 35% lower for women with the highest fifth of plasma α-carotene compared to that for subjects with the lowest quintile of α-carotene (odds ratio (OR) = 0.64, 95% confidence interval (CI): 0.47- 0.88; ptrend(p) = 0.01). Similar but less powerful results were found for β-carotene (OR = 0.73, CI: 0.53-1.02; p = 0.01), lutein/zeaxanthin (OR = 0.74, CI: 0.55-1.01; p = 0.04), and total carotenoids (OR = 0.76, CI: 0.55-1.05; p = 0.05). The inverse association observed between α-carotene intake and breast cancer was found to be greater for invasive cancers with nodal metastasis. The authors conclude that consumption of some carotenoids are inversely associated with the risk of breast cancer. However, although the association was strongest for α-carotene, the high degree of collinearity among the various carotenoids prevented them from concluding that this association was specific to any individual carotenoid.

The present population-based case-control study was designed to examine the associations between intake of carrots, spinach, and vitamin A in supplement form, and risk of breast cancer. Nine questions on food and supplement intake were used to assess intake of beta-carotene and vitamin A. The study was conducted in Maine, Massachusetts, New Hampshire, and Wisconsin during the period 1988 to 1991 and included 3,543 breast cancer cases and 9,406 cancer-free controls. Compared to no consumption of carrots or spinach, eating carrots or spinach more than twice weekly was found to be associated with a significantly lower risk of breast cancer (odds ratio = 0.56, 95% confidence interval: 0.34-0.91). However, no trend was found for estimated intake of preformed vitamin A from all evaluated foods and supplements. The authors commented that the data did not enable them to distinguish among possible explanations for the protective association observed between intake of carrots and spinach and risk of breast cancer.